The burden of HIV is ~60% higher in women than men in sub-Saharan Africa, and this gender inequity is a key challenge to HIV control. Identifying women at greatest risk for HIV and their infecting male partners is critical for effective, targeted control of the African HIV epidemic. It is also vital to identify those HIV-infected women most likely to contribute to ongoing viral spread. However, African women vastly underreport sexual contacts and high risk occupations such as sex work in interview-based surveys and clinical settings making their identification challenging. Here, we propose to use phylogenetic, epidemiological, and qualitative methods to study network drivers of female risk of HIV acquisition and onward transmission to men in the rural Rakai District, Uganda. We will use existing data from the Rakai Community Cohort Study (RCCS), a population- based study of HIV incidence and behaviors in 50 communities (n~17,000). In Aim 1 we will identify HIV- infected women who have central roles in transmission networks using viral phylogenetics and then characterize them with RCCS epidemiological data. We will also conduct in-depth interviews with these women to gain deeper insight into their HIV-related risks and to understand the barriers to reporting these risks. In Aim 2 we will use viral phylogenetics in conjunction with probabilistic statistical models to identify the pool of infecting male partners tat sustain the excess HIV burden among Rakai women. Lastly, in Aim 3 we will use microsimulation models to estimate the potential effectiveness of various combination HIV prevention strategies targeted to high risk subgroups to reduce HIV incidence. The proposed research is part of a K01 award and will provide the applicant with the advanced training in HIV modelling, behavioral science, and phylogenetics necessary to transition to an independent investigator with expertise in the application of interdisciplinary methods to HIV epidemiology and prevention. Results will improve female HIV risk assessment and identify candidate targeted strategies to prevent HIV in African women. It also will provide critical formative data fr a future R01 to implement and empirically assess the effectiveness of targeted interventions to high risk women and their partners in Rakai.